Despite the introduction of dozens of antipsychotic drugs during the past 50 years, there is evidence that the overall community functioning of individuals with schizophrenia has demonstrated relatively little improvement. This has led to the suggestion that the model of drug development for serious mentally illnesses is not working and should be replaced by new paradigm in which discoveries in basic neuroscience are translated into new and more innovative drugs. The overall goal of this R13 grant will be to facilitate this translation through a process that brings basic neuroscientists, neuropsychologists, and clinical investigators together to accomplish the following: (1) Identify novel molecular targets for improving treatments for domains of psychopathology in schizophrenia that contribute to the profound disability associated with this disorder (e.g., cognitive impairment, negative symptoms, refractory positive symptoms);(2) Identify biomarkers that will accelerate the process of drug discovery and development: (3) Use accumulated new information from recent NIMH initiatives and clinical trials to improve the design of clinical studies. This will be accomplished through a series of 3 meetings that will include experts in basic and clinical neuroscience from industry, academia, and government as well as representatives from the US Food and Drug Administration and consumer groups. The findings from each meeting will be rapidly disseminated to the field.